There is considerable evidence that non-transformed elements of the tumor microenvironment can play a substantial role in breast cancer progression and patient outcome. Cells of the monocyte/macrophage lineage comprise a significant portion of the breast tumor stroma, and are influential throughout the development of the tumor. A hallmark of these cells is their functional plasticity, which contributes to the fact hat tumor-associated macrophages (TAMs) have been shown to both support and inhibit tumor growth and metastasis. Adhesion signaling is used by macrophages for a variety of cellular functions, including chemotaxis, extravasation from blood vessels, and phagocytosis. The research component of this proposal will address the fundamental contribution of Focal Adhesion Kinase (FAK), a critical mediator of adhesion signaling and motility, to macrophage functions regulating primary breast tumor outgrowth. We will test the hypotheses that FAK plays a crucial role in facilitating migration of TAMs from the tumor vasculature to specified microdomains within the tumor microenvironment (Aim 1) and/or controls functions in macrophages that contribute to breast tumor control and progression (Aim 2). This research will provide new insights into the mechanisms driving breast tumor growth and raise new considerations for breast cancer treatments. The research component of this proposal will be supplemented with an active training plan that includes: (1) didactic coursework and training, (2) participation in research meetings and seminars, and (3) participation in scientific conferences. Together, the research and training plans will provide a strong foundation upon which to build a career as a successful, independent breast cancer researcher.